Ion Mobility Analysis of Lipoprotein Subfractions Identifies Three Independent Axes of Cardiovascular Risk.

Summary, in English

OBJECTIVE: Whereas epidemiological studies show that levels of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) predict incident cardiovascular disease (CVD), there is limited evidence relating lipoprotein subfractions and composite measures of subfractions to risk for CVD in prospective cohort studies. METHODS AND RESULTS: We tested whether combinations of lipoprotein subfractions independently predict CVD in a prospective cohort of 4594 initially healthy men and women (the Malmö Diet and Cancer Study, mean follow-up 12.2 years, 377 incident cardiovascular events). Plasma lipoproteins and lipoprotein subfractions were measured at baseline with a novel high-resolution ion mobility technique. Principal component analysis (PCA) of subfraction concentrations identified 3 major independent (ie, zero correlation) components of CVD risk, one representing LDL-associated risk, a second representing HDL-associated protection, and the third representing a pattern of decreased large HDL, increased small/medium LDL, and increased triglycerides. The last corresponds to the previously described "atherogenic lipoprotein phenotype." Several genes that may underlie this phenotype-CETP, LIPC, GALNT2, MLXIPL, APOA1/A5, LPL-are suggested by SNPs associated with the combination of small/medium LDL and large HDL. CONCLUSIONS: PCA on lipoprotein subfractions yielded three independent components of CVD risk. Genetic analyses suggest these components represent independent mechanistic pathways for development of CVD.

• Författare: Kiran Musunuru; Marju Orho-Melander; Michael P Caulfield; Shuguang Li; Wael A Salameh; Richard E Reitz; Göran Berglund; Bo Hedblad; Gunnar Engström; Paul T Williams; Sekar Kathiresan; Olle Melander; Ronald M Krauss
• Avdelning/ar: Institutionen för kliniska vetenskaper, Malmö; Internmedicin - epidemiologi; Kardiovaskulär forskning - epidemiologi; Kardiovaskulär forskning - hypertoni
• Publiceringsår: 2009
• Språk: Engelska
• Sidor: 628-1975
• Publikation/Tidskrift/Serie: Arteriosclerosis, Thrombosis and Vascular Biology
• Volym: 29
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/19729614?dopt=Abstract; http://dx.doi.org/10.1161/ATVBAHA.109.190405
• Dokumenttyp: Artikel i tidskrift
• Förlag: Lippincott Williams & Wilkins
• Ämne: Cardiac and Cardiovascular Systems
• Status: Published
• Forskningsgrupp: Internal Medicine - Epidemiology; Cardiovascular Research - Epidemiology; Cardiovascular Research - Hypertension
• ISBN/ISSN/Övrigt: ISSN: 1524-4636